Brain systems that participate in object and spatial vision and in working and long-term visual memory were investigated in healthy young men by measuring regional cerebral blood flow (rCBF) with positron emission tomography (PET) and H2150. The results identified dorsolateral occipital and superior parietal areas activated more by spatial visual processing, and ventral occipital and occipitotemporal areas activated more by object discrimination. Old subjects demonstrated rCBF activations in the same regions as did young subjects, but also demonstrated activation of ventral areas during spatial vision and dorsal areas during object vision, suggesting less functional separation of these visual systems. Patients with dementia of the Alzheimer type (DAT) who could perform an object vision task, demonstrated normal percent baseline activation of rCBF in occipitotemporal cortex during the task, suggesting preserved capacity to recruit this area for perceptual processing. Memory-related modulations of cortical rCBF were found in anterior temporal and prefrontal cortex in DAT patients. Rate of cognitive decline was significantly correlated with rate of brain tissue loss (atrophy) with serial computer-assisted tomography (CT) scans, and with rate of worsening abnormality of resting state regional cerebral metabolic rates for glucose (rCMRglc) as measured by PET and 18F-Fluoro-2-deoxyglucose. Two patterns of cerebral metabolism characteristic of DAT were identified using regional covariance analysis of resting state rCMRglc. These patterns were correlated with specific cognitive deficits. Premorbid intellectual ability was inversely correlated with rCMRglc in several regions of association cortex in DAT patients. Among DAT patients, early age at onset of dementia was related to greater impairment on a measure of visuospatial attention. DAT patients with a family history of dementia showed deficits in rCMRglc of the anterior association regions. A unique neuropsychological profile was observed for a subgroup of DAT patients with early prominent visual disturbances. Older Down syndrome adults perform worse on mental abilities tests than do younger subjects with immediate memory and language less affected by age in Down syndrome than long-term memory and visuospatial function.